Physical Motif Clustering within Intrinsically Disordered Nucleoporin Sequences Reveals Universal Functional Features
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{"title"=>"Physical Motif Clustering within Intrinsically Disordered Nucleoporin Sequences Reveals Universal Functional Features", "type"=>"journal", "authors"=>[{"first_name"=>"David", "last_name"=>"Ando", "scopus_author_id"=>"55855783400"}, {"first_name"=>"Michael", "last_name"=>"Colvin", "scopus_author_id"=>"7005251947"}, {"first_name"=>"Michael", "last_name"=>"Rexach", "scopus_author_id"=>"6603952594"}, {"first_name"=>"Ajay", "last_name"=>"Gopinathan", "scopus_author_id"=>"6602302196"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"24066078", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0073831", "pui"=>"369822383", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84884199740", "sgr"=>"84884199740"}, "id"=>"1d16a481-e872-38b8-b344-389504c7b3c9", "abstract"=>"Bioinformatics of disordered proteins is especially challenging given high mutation rates for homologous proteins and that functionality may not be strongly related to sequence. Here we have performed a novel bioinformatic analysis, based on the spatial clustering of physically relevant features such as binding motifs and charges within disordered proteins, on thousands of Nuclear Pore Complex (NPC) FG motif containing proteins (FG nups). The biophysical mechanism by which FG nups regulate nucleocytoplasmic transport has remained elusive. Our analysis revealed a set of highly conserved spatial features in the sequence structure of individual FG nups, such as the separation, localization, and ordering of FG motifs and charged residues along the protein chain. These functionally conserved features provide insight into the particular biophysical mechanisms responsible for regulation of nucleocytoplasmic traffic in the NPC, strongly constraining current models. Additionally this method allows us to identify potentially functionally analogous disordered proteins across distantly related species.", "link"=>"http://www.mendeley.com/research/physical-motif-clustering-within-intrinsically-disordered-nucleoporin-sequences-reveals-universal-fu", "reader_count"=>32, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>7, "Student > Ph. D. Student"=>8, "Student > Master"=>7, "Other"=>1, "Student > Bachelor"=>4, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>7, "Student > Ph. D. Student"=>8, "Student > Master"=>7, "Other"=>1, "Student > Bachelor"=>4, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>1, "Materials Science"=>1, "Agricultural and Biological Sciences"=>16, "Physics and Astronomy"=>4, "Chemistry"=>3, "Computer Science"=>1, "Earth and Planetary Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Materials Science"=>{"Materials Science"=>1}, "Chemistry"=>{"Chemistry"=>3}, "Physics and Astronomy"=>{"Physics and Astronomy"=>4}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"United States"=>2, "Japan"=>1, "Switzerland"=>1, "Germany"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1206068"], "description"=>"<p>(A) The FG clusters and charge clusters of an example FG nup sequence. (B) Percent overlap of FG clusters with charge clusters (blue). Almost 80 percent of FG motif cluster regions have zero overlap with clusters of charges. Other percentages of overlap, while strongly in the minority, appear with roughly equal probability. FG nups which have been randomly shuffled (in red) have 4 percent of their FG motif cluster regions completely disjoint from charge clusters while there is a strong tendency for FG clusters to overlap with charge clusters with a most probable frequency overlap at 45 percent. Inset shows statistical significance of degree of overlap for FG nups (top, blue) versus WG/FG control group (bottom, red). Horizontal axis in inset shows the deviation of the percent overlap from the mean value for the randomly shuffled ensemble measured in units of the standard deviation of the random ensemble distribution. (B) Histogram of the topological complexity of FG nups (in blue) and randomly shuffled nups (in red). A majority of FG nups (66%) have a low topological complexity (less than 4) with 34% being purely diblock charge-FG copolymer structure, while randomly shuffled nups have only a small minority (22%) with low topological complexity and only 2% are diblocks. Upper inset shows that 77% of FG nups have a topological complexity which is less than their random ensemble by more than one standard deviation, while the control group shows little deviation from the ensemble (red, lower inset).</p>", "links"=>[], "tags"=>["fg"], "article_id"=>800696, "categories"=>["Biological Sciences", "Information And Computing Sciences"], "users"=>["David Ando", "Michael Colvin", "Michael Rexach", "Ajay Gopinathan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0073831.g001", "stats"=>{"downloads"=>5, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spatial_relationship_between_FG_and_charge_clusters_/800696", "title"=>"Spatial relationship between FG and charge clusters.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-16 02:45:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206076"], "description"=>"<p>Example proteins from <i>S. cerevisiae</i> (‘y’ prefix) and humans (‘h’ prefix) for each functional clustering group. Boxed in green are example proteins with low overlap between FG and charge clusters and a topological complexity of 3. In the yellow box are example proteins with low toplogical complexity and diblock structure, the first clustering group described in the text. Example proteins from the last clustering group described in the text are boxed in red at the bottom, with these proteins displaying high overlap and high levels of topological complexity (Nup153 sequence reversed to ease comparison with Nsp1).</p>", "links"=>[], "tags"=>["homologous"], "article_id"=>800704, "categories"=>["Biological Sciences", "Information And Computing Sciences"], "users"=>["David Ando", "Michael Colvin", "Michael Rexach", "Ajay Gopinathan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0073831.g004", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_homologous_proteins_/800704", "title"=>"Identification of homologous proteins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-16 02:45:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206074"], "description"=>"<p>(A) Effects of successively including observed sequence constraints. These constraints start from a typical randomly shuffled sequence at the very top with the pink bar representing the entire linear AA sequence. Blue blocks represent FG clusters, red blocks represent clusters of charged AAs, gray represents overlap between cluster types, green shaded regions represent folded domains which anchor to the NPC wall, while disordered domains are represented by visually solvated pixelation. The arrows originating from the starting sequence represent a possible manner by which imposing the constraint of disjointness would result in a new sequence. Similarly the successive arrows represent the imposition of further constraints found in this paper, from the low topological complexity, to the FG-Charge polarity, to the Folded-Disordered polarity, to the net charge of domains, finally culminating in an average inference which is representative of FG nups. (B) The spatial distribution of FG motifs and charged AAs for all known FG nups of S. cerevisiae plotted as motif/AA, averaged over 20 nearest AAs. Regions of high FG motif density are shown in pink while regions of low charge density, also in pink, correspond spatially throughout the sequences of these nups. Regions of protein which are predicted to form folded structures by the PONDR algorithm are highlighted with grey bars, and known/predicted <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073831#pone.0073831-Denning1\" target=\"_blank\">[16]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073831#pone.0073831-Yamada1\" target=\"_blank\">[26]</a> anchor domains circled with green ovals.</p>", "links"=>[], "tags"=>["fg", "nup"], "article_id"=>800702, "categories"=>["Biological Sciences", "Information And Computing Sciences"], "users"=>["David Ando", "Michael Colvin", "Michael Rexach", "Ajay Gopinathan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0073831.g003", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Consensus_FG_nup_structure_/800702", "title"=>"Consensus FG nup structure.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-16 02:45:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206106", "https://ndownloader.figshare.com/files/1206107", "https://ndownloader.figshare.com/files/1206108", "https://ndownloader.figshare.com/files/1206109", "https://ndownloader.figshare.com/files/1206110", "https://ndownloader.figshare.com/files/1206111", "https://ndownloader.figshare.com/files/1206113", "https://ndownloader.figshare.com/files/1206115", "https://ndownloader.figshare.com/files/1206116", "https://ndownloader.figshare.com/files/1206118", "https://ndownloader.figshare.com/files/1206120", "https://ndownloader.figshare.com/files/1206121", "https://ndownloader.figshare.com/files/1206122", "https://ndownloader.figshare.com/files/1206123", "https://ndownloader.figshare.com/files/1206124", "https://ndownloader.figshare.com/files/1206125", "https://ndownloader.figshare.com/files/1206126", "https://ndownloader.figshare.com/files/1206127", "https://ndownloader.figshare.com/files/1206128", "https://ndownloader.figshare.com/files/1206129"], "description"=>"<div><p>Bioinformatics of disordered proteins is especially challenging given high mutation rates for homologous proteins and that functionality may not be strongly related to sequence. Here we have performed a novel bioinformatic analysis, based on the spatial clustering of physically relevant features such as binding motifs and charges within disordered proteins, on thousands of Nuclear Pore Complex (NPC) FG motif containing proteins (FG nups). The biophysical mechanism by which FG nups regulate nucleocytoplasmic transport has remained elusive. Our analysis revealed a set of highly conserved spatial features in the sequence structure of individual FG nups, such as the separation, localization, and ordering of FG motifs and charged residues along the protein chain. These functionally conserved features provide insight into the particular biophysical mechanisms responsible for regulation of nucleocytoplasmic traffic in the NPC, strongly constraining current models. Additionally this method allows us to identify potentially functionally analogous disordered proteins across distantly related species.</p></div>", "links"=>[], "tags"=>["motif", "clustering", "intrinsically", "disordered", "nucleoporin", "sequences", "reveals"], "article_id"=>800728, "categories"=>["Biological Sciences", "Information And Computing Sciences"], "users"=>["David Ando", "Michael Colvin", "Michael Rexach", "Ajay Gopinathan"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0073831.s001", "https://dx.doi.org/10.1371/journal.pone.0073831.s002", "https://dx.doi.org/10.1371/journal.pone.0073831.s003", "https://dx.doi.org/10.1371/journal.pone.0073831.s004", "https://dx.doi.org/10.1371/journal.pone.0073831.s005", "https://dx.doi.org/10.1371/journal.pone.0073831.s006", "https://dx.doi.org/10.1371/journal.pone.0073831.s007", "https://dx.doi.org/10.1371/journal.pone.0073831.s008", "https://dx.doi.org/10.1371/journal.pone.0073831.s009", "https://dx.doi.org/10.1371/journal.pone.0073831.s010", "https://dx.doi.org/10.1371/journal.pone.0073831.s011", "https://dx.doi.org/10.1371/journal.pone.0073831.s012", "https://dx.doi.org/10.1371/journal.pone.0073831.s013", "https://dx.doi.org/10.1371/journal.pone.0073831.s014", "https://dx.doi.org/10.1371/journal.pone.0073831.s015", "https://dx.doi.org/10.1371/journal.pone.0073831.s016", "https://dx.doi.org/10.1371/journal.pone.0073831.s017", "https://dx.doi.org/10.1371/journal.pone.0073831.s018", "https://dx.doi.org/10.1371/journal.pone.0073831.s019", "https://dx.doi.org/10.1371/journal.pone.0073831.s020"], "stats"=>{"downloads"=>23, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Physical_Motif_Clustering_within_Intrinsically_Disordered_Nucleoporin_Sequences_Reveals_Universal_Functional_Features_/800728", "title"=>"Physical Motif Clustering within Intrinsically Disordered Nucleoporin Sequences Reveals Universal Functional Features", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-09-16 02:45:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/1206070"], "description"=>"<p>(A) Polarity between charge and FG regions. FG nups (blue) tend to adopt a large negative and well conserved value for N-terminus to C-terminus polarity. Randomly shuffled FG nups showed no overall average polarity (red) and the statistical significance of FG nup polarity was consistently higher than three standard deviations (inset, blue, upper). The control group did not show a considerable difference from the random ensemble (inset, red, lower). (B) Polarity between disordered and folded regions (blue) using the PONDR <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073831#pone.0073831-Xue1\" target=\"_blank\">[22]</a> protein disorder predictor. Observed polarities are on average similar to FG to charge cluster polarities, . Interestingly, values for the disordered regions alone (green) show a similar trend. Inset shows the net charge of folded structural nups/kaps (blue) and FG clusters (green) which appear to be equal and opposite on the whole, while disordered charge cluster regions (red dashed) appear to be net neutral. Histogram values for net charges for charge clusters greater than 0.1 e/AA and less than −0.1 e/AA are negligible and are shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073831#pone.0073831.s020\" target=\"_blank\">Text S1</a>.</p>", "links"=>[], "tags"=>["charges", "fg"], "article_id"=>800698, "categories"=>["Biological Sciences", "Information And Computing Sciences"], "users"=>["David Ando", "Michael Colvin", "Michael Rexach", "Ajay Gopinathan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0073831.g002", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Polarity_and_charges_of_FG_nups_/800698", "title"=>"Polarity and charges of FG nups.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-16 02:45:55"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Molecular biology", "average_usage"=>[272, 466, 589, 702, 806, 903, 995, 1086, 1176, 1258, 1347, 1422, 1493]}, {"subject_area"=>"/Physical sciences/Mathematics", "average_usage"=>[259, 431, 541, 639, 727, 816, 898, 980, 1061, 1136, 1214, 1294, 1356]}]}
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